INFECTION WITH LISTERIA-MONOCYTOGENES IMPAIRS SIALIC-ACID ADDITION TOHOST-CELL GLYCOPROTEINS

Listeria monocytogenes is a facultative intracellular bacterium that c auses severe disease in neonates and immunocompromised adults. Althoug h entry, multiplication, and locomotion of Listeria in the cytosol of infected cells are well described, the impact of such infection on the host cell is unknown. In this report, we investigate the effect oft. monocytogenes infection on MHC class I synthesis, processing, and intr acellular trafficking. We show that L. monocytogenes infection interfe res with normal processing of N-linked oligosaccharides on the major h istocompatibility complex (MHC) class I heavy chain molecule, H-2K(d), resulting in a reduced sialic acid content. The glycosylation defect is more pronounced as the infection progresses and results from interf erence with the addition of sialic acid rather than its removal by a n euraminidase. The effect is found in two different cell lines and is n ot limited to MHC class I molecules since CD45, a surface glycoprotein , and LGP120, a lysosomal glycoprotein, are similarly affected by L. m onocytogenes infection. The glycosylation defect is specific for infec tion by L. monocytogenes since neither Trypanosoma cruzi nor Yersinia enterocolitica, two other intracellular pathogens, reproduces the effe ct. The resultant hyposialylation of H-2K(d) does not impair its surfa ce expression in infected cells. Diminished sialic acid content of sur face glycoproteins may enhance host-defense by increasing susceptibili ty to lysis and promoting clearance of Listeria-infected cells.